Chromatography columns provide a means for separating, purifying and isolating chemical and biological compounds. The size and type of column used in these operations typically depends upon the scale of the process in question, small glass or plastic walled columns typically being used for research purposes, while larger metal columns are employed for industrial processes. For instance, chromatography columns may be used in manufacturing processes to purify process liquids and separate substances of interest from such liquids; typical examples include large-scale preparative purification of fine chemicals and pharmaceuticals, together with biological products.
Whilst the present invention relates to both glass/plastic walled and larger metal walled chromatography columns, it is particularly useful for manufacturing and industrial-scale chromatography columns.
Industrial-scale chromatography columns typically comprise a hollow, axially vertical tubular housing including a liquid inlet at the upper end and through which the buffer and substances to be separated are dispensed to the media bed located within the cavity of the tube, and a liquid collecting system at the lower end for collecting substances and buffer. The particulate chromatographic media or bed through which the buffer fluid and/or substances to be separated and purified percolates is located between the liquid inlet and collecting system.
An adapter assembly is typically affixed to the upper end of the tubular housing and a base assembly to the lower end where it is bolted to the bottom flanges. Each of these assemblies typically comprises a strong backing plate and a distributor plate which further supports a bed support; a bed support is a layer of mesh, screen, filter, sinter or other fluid-permeable media-retaining material which permits process liquid flow into and out of the chromatography bed space or cavity while retaining the bed of particulate medium. To provide adjustability and control of the bed height and bed compression, the adapter assembly is typically made in the form of a piston or sliding adapter in the column tube interior. After the column is charged with bed media, typically through a valve or nozzle, the adapter may be forced toward the bottom of the tube to compress or pressurize the media bed. Generally the base assembly is a fixed structure which is bolted against the bottom flange of the column tube but, in some instances, may also be in the form of a movably slidable piston or adapter.
The backing plate of the base assembly generally acts as a support for the column, being itself supported on legs or some other stand arrangement which allows clearance for outlet pipework projecting beneath the base assembly.
A problem often encountered in the use of both laboratory and industrial-scale chromatography columns is the leakage of liquid, such as buffer or mobile phase, or particulate media material, from the bed space or cavity past the adapter or piston. Seals, such as O-rings, are commonly used to prevent such leakage but these tend to perform poorly under operating conditions due to abrasion and inadequate sealing. The resulting leakage can lead to poor chromatographic performance due to liquid losses and also to bacterial contamination where liquid collects in dead spaces between the O-ring and the adapter wall.
U.S. Pat. No. 5,671,928 describes a seal for small, glass or plastic walled columns which is claimed to provide good releasability and sealing capabilities, allows visual inspection that a seal has been made, increased chromatographic efficiency and a substantial reduction in bacterial growth. However, the seals disclosed in U.S. Pat. No. 5,671,928 are made from a resilient seal material such as rubber that require a coating with a friction-reducing polymer such as polytetrafluoroethylene to reduce abrasion. Such coatings are difficult to apply and tend not to be permanent in nature. Furthermore, the seals described in this document are self-compensating to the extent that an increase in pressure increases the sealing force. Such a design can cause problems due to the resulting increased friction and abrasion.
There is thus a need to provide improved seals for use in chromatography columns in order to maintain high levels of chromatographic performance under normal packing and operating pressures. Preferably the seals should be flexible enough for use in a range of columns to obviate the need for high levels of tolerance in manufacturing the internal column walls. In addition to preventing leakage of buffer or liquid from the bed space past the adapter or piston, thereby reducing microbiological contamination, such seals should preferably be capable of cleaning, removing and compressing particulate media from the internal walls of the column to aid the packing process and further reduce the risk of leakage. Furthermore, the seals should be stable across the temperature ranges under which the chromatographic column is required to operate.